Hematological, cardio-pulmonary, and biochemical effects of acute (7 days) and chronic (14 weeks) exposure to hypoxia (T=22 C, P02=80 Torr), cold (Ta=5 C, P02=133 Torr), and cold + hypoxia (Ta =5 Ca, P02=80 Torr) will be investigated in guinea pigs (Cavia porcellus). A control group of animals will be studied under the ambient conditions of our laboratory in Denver (Ta=22 C, PO2=133 Torr). The proposed study is designed to duplicate the recently reported observation that cold blunts the hematological response to hypoxia, and to understand the mechanisms involved in controlling and modulating the hematological response to these environmental stresses. The specific aims include: a) determination of the time course and magnitude of changes in circulating erythropoietin (Ep) with an in vitro Ep bioassay; b) evaluation of the erythropoietic response by measurement of Hct and [Hb], and determination of red cell mass and plasma volume, by examination of tissue cultures, and by counting blood cell types in tissues and whole blood; c) evaluates of other factors, namely catecholamines, growth and thyroid hormones, testosterone, iron uptake and storage sites, and red cell survival, which may influence the level of erythrocytosis; d) evaluation of 02 transport and delivery to tissues by measurement of arterial and venous PO2, PCO2, PH, and oxygen contents, red cell 2,3-DPG, and Hb-O2 dissociation curves (P50's); e) assessment of respiratory effects by measurement of VO2, VCO2, VE, VT, and frequency of respiration; f) assessment of cardio-vascular effects by measurement of cardiac output, heart rate, aortic and pulmonary blood pressures, and heart weights; g) assessment of suitability of the guinea pig as an animal model for Chronic Mountain Sickness (CMS). CMS is a clinical condition characterized by exaggerated erythrocytosis and occasional right heart failure which occurs in some individuals native to high altitude who "lose" their adaptation. Guinea pigs may be a good animal model for the study of CMS as they develop a clinical condition when exposed to high altitude conditions similar to that observed in humans. This model may also be applicable to the understanding of the pathogenesis of cor pulmonale which is characterized by enlargement of the right ventricle, secondary to long standing lung disease, usually occurring with chronic hypoxia and erythrocytosis. In addition, this research may provide new avenues for the treatment of these conditions.